Training the Innate Immune System Against SARS-CoV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents

Corona Virus Infection Clinical Trial

— NH-Shingrix  

Official title:

Training the Innate Immune System Against SARS-COV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents: A Randomized, Doubled-Blinded, Comparative Group Observational Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04523246
• Other study ID #: 12394
• Status: Completed
• Phase: Early Phase 1
• Start date: September 1, 2020
• Est. completion date: May 19, 2023

Study information

• Verified date: November 2023
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure the effect of the Shingrix vaccine on your immune system and whether that has any effect on the body's ability to fight off other infections such as COVID-19. We hypothesize that: H1: Shingrix vaccination will elevate acute and trained immunity H2: For 6 months following the first injection, increased levels of acute and trained immunity is associated with less disease, including fewer hospitalizations and deaths associated with flu, pneumonia, and COVID-19.

Description:

The purpose of this pilot study is to provide preliminary data in support of the concept that training of the innate immune system occurs following immunization (2 doses ,3 months apart) with the Shingrix vaccine as compared to placebo (normal saline) in older adults residing in nursing homes. Two hundred nursing home residents, both men and women, aged >65 years, who have not acquired COVID-19 (verified through a screening questionnaire and by both viral antigen and antibody testing at the screen and least one week before the first injection) will get two intramuscular injections containing either the Shingrix vaccine, and the other half, two injections containing a normal saline (placebo comparison) approximately three months apart. Blood samples are collected before the baseline injection (day zero), 1 day after the second injection (91 days post) and 1 month following the second injection (120 days). Weekly symptom checks and monthly antibody testing around day 180- will identify residents with COVID-19 and the severity of COVID-19 symptoms. The primary outcome is the difference in immune cell capacity to produce type I interferon, interferon associated molecules, and proinflammatory mediators after receiving a 2 injection series of the Shingrix vaccine versus normal saline. Secondary outcomes include differences in hospitalization, pulmonary infections, and positive COVID-19 cases (via antibody testing on days 90, 120, and 180) in the Shingrix and normal saline groups. We anticipate that residents receiving the Shingrix vaccine will demonstrate signs of "trained" immunity compared to a control group receiving saline injections.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: May 19, 2023
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Meet Centers for Medicare and Medicaid definition for Long term care resident.

2. 65 years and older.

3. Have already received or provide consent to receive the 2020 flu vaccine.

4. Negative screen (within the last 2 weeks) for COVID 19 virus.

5. Has a history of chickenpox or shingles.

6. Able to read and speak English.

7. Able to provide informed consent and assent (with guardian/health care proxy).

Exclusion Criteria:

1. Brief Interview of Mental Status (BIMS) score <8 (indicating severe dementia).

2. Prior vaccination with the Shingrix.

3. Positive test for COVID 19 or prior history of COVID 19 infection.

4. Conditions that confound the interpretation of the innate immune measures. (i.e. Terminal condition, receiving hospice, Stage 3 and 4 open wound, Chemotherapy, immune modulators or other immunosuppressants, autoimmune disorders, and BMI < 20 kg/m2).

5. Conditions that confound interpretation of respiratory symptoms. (i.e Ventilator dependent, receiving more that 2-3 liters/min of oxygen by nasal cannula, chronic diarrhea, recurrent infections).

Related Conditions & MeSH terms

• Allergy and Immunology
• Corona Virus Infection
• Coronavirus Infections
• Herpes Zoster
• Virus Diseases

Intervention

Biological:
• SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted)
The Shingrix vaccine is a subunit vaccine that contains the recombinant varicella zoster virus (VZV) glycoprotein E (gE), adjuvanted with the proprietary Adjuvant System (AS01B). The AS01B Adjuvant system consists of two immune-stimulants, the saponin, Quillaja saponaria Molina, fraction 21 (QS21), and the toll-like receptor 4 (TLR4) agonist, MPL (3-O-desacyl-40-MPL) that enhance the release of interferon gamma (IFN?), which in turn stimulates activation and recruitment of blood monocyte-derived and resident lymph node dendritic cells to take up and present gE to cluster of differentiation 4 (CD4+) T cells.

Drug:
• Normal Saline
Sterile normal saline, inactive control.

Locations

Country	Name	City	State
United States	Fran and Earl Ziegler College of Nursing	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
University of Oklahoma	Oklahoma Medical Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evidenced of active and trained innate immunity	The primary outcome is change in the release of Type I interferon, interferon gamma, interferon associated molecules, and proinflammatory mediators released from monocytes/macrophages and natural killer cells (including gene activation) after receiving 2 injections of the Shingrix vaccine versus normal saline.	Day 91 and 120 (post vaccination)
Secondary	Respiratory Disease Severity (6 month)	cases ( nasal swab for viral antigen and antibody testing), symptoms (symptom checklist), hospitalizations (MDS 3.0 report/chart reviews) and deaths (MDS 3.0 report/chart reviews) associated with flu, pneumonia, and COVID-19.	Days 120 through 180